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Infection and Immunity, August 2009, p. 3485-3490, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.01573-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Streptococcus mitis Phage-Encoded Adhesins Mediate Attachment to {alpha}2-8-Linked Sialic Acid Residues on Platelet Membrane Gangliosides{triangledown}

Jennifer Mitchell and Paul M. Sullam*

San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California 94121

Received 26 December 2008/ Returned for modification 31 January 2009/ Accepted 28 May 2009

The direct binding of bacteria to human platelets contributes to the pathogenesis of infective endocarditis. Platelet binding by Streptococcus mitis strain SF100 is mediated in part by two bacteriophage-encoded proteins, PblA and PblB. However, the platelet membrane receptor for these adhesins has been unknown. In this study, we demonstrate that these proteins mediate attachment of bacterial cells to sialylated gangliosides on the platelet cell surface. Desialylation of human platelet monolayers reduced adherence of SF100, whereas treatment of the platelets with N- or O-glycanases did not affect platelet binding. Treatment of platelets with sialidases having different linkage specificities showed that removal of {alpha}2-8-linked sialic acids resulted in a marked reduction in bacterial binding. Preincubation of SF100 with ganglioside GD3, a glycolipid containing {alpha}2-8-linked sialic acids that is present on platelet membranes, blocked subsequent binding of this strain to these cells. In contrast, GD3 had no effect on the residual binding of platelets by strain PS344, an isogenic {Delta}pblA {Delta}pblB mutant. Preincubating platelets with specific monoclonal antibodies to ganglioside GD3 also inhibited binding of SF100 to platelets, but again, they had no effect on binding by PS344. When the direct binding of S. mitis strains SF100 and PS344 to immobilized gangliosides was tested, binding of PS344 to GD3 was reduced by 70% compared to the parent strain. These results indicated that platelet binding by SF100 is mediated by the interaction of PblA and PblB with {alpha}2-8-linked sialic acids on ganglioside GD3.

* Corresponding author. Mailing address: Division of Infectious Diseases, VA Medical Center (111W), 4150 Clement Street, San Francisco, CA 94121. Phone: (415) 221-4810, ext. 2550. Fax: (415) 750-6951. E-mail: paul.sullam{at}ucsf.edu

{triangledown} Published ahead of print on 8 June 2009.

Editor: A. Camilli

Infection and Immunity, August 2009, p. 3485-3490, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.01573-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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